Systems and methods for treating eye diseases using retrograde blood flow

ABSTRACT

A method, device, or system for treating eye disorders or conditions, comprising restoring or increasing blood flow or blood flow rate in an artery that supplies blood to or in the eye, thereby increasing the amount of nutrient(s) that reaches the eye or a portion thereof. The invention also includes methods, devices, or systems for treating eye disorders or conditions which use reverse flow or retrograde flow structures and systems during the treatment of the eye disease.

FIELD OF THE INVENTION

The present invention relates to treating eye diseases and conditions.

BACKGROUND OF THE INVENTION

Diseases of the eye, specifically age-related macular degeneration(AMD), glaucoma and diabetic retinopathy affect a large percentage ofthe population. In part, most of the diseases of the eye are treated bytreating one or more symptoms, but failing to address the underlyingcause(s) of the disease or condition. These therapies are thereforedeficient in one or more aspects, necessitating improved approaches.

In a general sense, the pathogenesis of some of these eye diseases issimilar if not the same as those seen for cardiac diseases and forabdominal aorta conditions. However, the anatomy of the vasculaturebehind the eye is typically smaller, includes more branches, andincludes more sharp angles in the blood flow pathway. Further, thevascular system supplying blood to the eye is closer to the brain; anyuncaptured or non-rerouted debris may cause an immediate stroke.

The use of catheter delivery systems for positioning and deployingtherapeutic devices, such as balloons, stents and embolic devices, inthe vasculature of the human body has become a standard procedure fortreating endovascular diseases. It has been found that such devices areparticularly useful as an alternative in treating areas wheretraditional operational procedures are impossible or pose a great riskto the patient. Some of the advantages of catheter delivery systems arethat they provide methods for treating blood vessels by an approach thathas been found to reduce the risk of trauma to the surrounding tissue,and they also allow for treatment of blood vessels that in the pastwould have been considered inoperable.

BRIEF SUMMARY OF THE INVENTION

In accordance with the present invention, diseases and conditions of theeye may be directly mediated by compromised blood flow to thevasculature of the eye. The present invention treats eye diseases byrestoring blood flow using a reverse flow or retrograde flow device andsystem.

In a reverse flow embolic protection method, an arterial access cannulais connected to a venous cannula in order to establish a reverse orretrograde flow from an artery (such as the internal carotid arteryand/or ophthalmic artery) through the arterial cannula and away from theeye and/or vasculature of the eye. Flow in an artery is occluded,typically by inflating a balloon on the distal tip of the cannula, in acarotid artery, the internal carotid artery (ICA), or the ophthalmicartery (OA), thereby reversing blood flow in the ICA and/or the OA.After such reverse or retrograde flow is established, any catheter orinterventional procedure in the ophthalmic artery can be performed witha greatly reduced risk of emboli entering the eye.

The present invention is also directed to one or more intravascularmedical devices and methods intended to sufficiently unblock orpartially restore blood flow in a blocked or partially blocked arterysuch that nutrient(s) content is increased distal to the blockage. Anembodiment of the invention is directed to devices and methods forrestoring blood flow through the ostium. An embodiment of the inventionincludes using these devices and methods to restore or increase bloodflow to the eye or a portion thereof. An embodiment of the inventionincludes restoring or increasing nutrient levels in the eye or a portionthereof. Restoring or increasing blood flow may include using thesedevices and methods, or equivalent devices and methods, but is not to belimited thereby.

The inventors believe that any blockage or reduction in fluid or bloodflow is a mediator of certain consequences described more particularlybelow. As used herein, blockage refers to complete or partial blockage;reduced, restricted, or eliminated blood flow; sometimes caused byplaque, tortuous shaped anatomy, vessel failure or dysfunction.

While not intending to be restricted to any particular theory ofoperation, function, or causal connection, the inventors believe anycondition, such as a blockage, that leads to lowered nutrientavailability and/or consumption is a direct mediator of normalphysiologic function. The inventors also believe that those conditionsalso mediate metabolic waste removal from cells, organs, and otherbiological structures.

Possible conditions include but are not limited to one or more of thefollowing: reduced or blocked blood flow in one or more arteries orsystem of arteries; reduced or blocked source of energy or nutrients toa cell, organelle of a cell; mitochondrion; group of cells, or organ;altered aerobic energy metabolism; altered mitochondria oxidativephosphorylation; decreased or blocked supply of glucose; decreasedhemoglobin amount or delivery to one or more intra-cranial structures orto one or more eye tissues; reduced blood flow or rate anywhere in thefluid flow path between the ICA and eye tissue; and any blockage orpartial blockage in one or more arteries or system of arteries; anymediation of the complement system, the complement cascade, and/or oneof the complement cascade associated molecules; and lowered/blockednutrient supply and/or metabolic waste removal is implicated, andtherefore may mediate one or more diseases, disorders, or biologicalfunction.

These conditions may occur in one or more of the following areas orstructures: one or more arteries; one or more cranial arteries; and oneor more arteries associated with of supplying blood flow to the eye; theinternal carotid artery; the ophthalmic artery; anywhere in the fluidflow path between the ICA and eye tissue; the junction between the ICAand the OA, which is referred to in this disclosure as the ostium; andsecondary areas of the anatomy include the vascular system commonlyreferred to as the terminal branches. These areas include, but are notlimited to the Supra orbital Artery (SOA), the Supra Trochlear Artery(STA), the dorsal Nasal Artery (DNA), and the facial Arteries (FA); anycranial artery; and in any of the junctions or ostia between any of thevasculature between the ICA and one or more eye tissues.

Examples of diseases and conditions include, but are not limited to, anyof a variety of eye diseases, including but not limited to AMD (both dryand wet); neuronal cell death; Alzheimer's disease; dementia; glaucoma;diabetic macula edema, macular telangiectasia (e.g., type 1 or 2 maculartelangiectasia), atrophic macular degeneration, chorioretinopathy (e.g.,central serous chorioretinopathy), retinal inflammatory vasculopathy,pathological retinal angiogenesis, age-related maculopathy,retinoblastoma, Pseudoxanthoma elasticum, a vitreoretinal disease,choroidal sub-retinal neovascularization, central serouschorioretinopathy, ischemic retinopathy, hypertensive retinopathy ordiabetic retinopathy (e.g., nonproliferative or proliferative diabeticretinopathy, such as macular edema or macular ischemia), retinopathy ofprematurity (e.g., associated with abnormal growth of blood vessels inthe vascular bed supporting the developing retina), venous occlusivedisease (e.g., a retinal vein occlusion, branch retinal vein occlusionor central retinal vein occlusion), arterial occlusive disease (e.g.,branch retinal artery occlusion (BRAO), central retinal artery occlusionor ocular ischemic syndrome), central serous chorioretinopathy (CSC),cystoid macular edema (CME) (e.g., affecting the central retina ormacula, or after cataract surgery), retinal telangiectasia (e.g.,characterized by dilation and tortuosity of retinal vessels andformation of multiple aneurysms, idiopathic JXT, Leber's miliaryaneurysms, or Coats' disease), arterial macroaneurysm, retinalangiomatosis, radiation-induced retinopathy (RIRP), or rubeosis iridis(e.g., associated with the formation of neovascular glaucoma, diabeticretinopathy, central retinal vein occlusion, ocular ischemic syndrome,or chronic retinal detachment); distortions and/or blind spots(scotoma); changes in dark adaptation (diagnostic of rod cell health);changes in color interpretation (diagnostic of cone cell health);decrease in visual acuity; cataract (e.g., age-related cataract).

Methods and devices are also described for ophthalmic arteryinterventional procedures, such as stenting, angioplasty, andatherectomy, performed through a transcervical or transfemoral approachinto the ophthalmic artery, either using an open surgical technique orusing a percutaneous technique, such as a modified Seldinger technique.Some of these methods and devices are particularly useful in procedureswhich use reverse or retrograde flow protocols.

These disclosed methods and devices include arterial access sheaths,closure devices, and interventional catheters. These methods and devicesare useful for procedures utilizing any method of embolic protection,including distal filters, flow occlusion, retrograde flow, orcombinations of these methods, or for procedures which do not use anymethod of embolic protection. Specific methods and devices for embolicprotection are also described.

In particular, methods and devices are disclosed for enabling retrogradeor reverse flow blood circulation in the ophthalmic artery in order tolimit or prevent the release of emboli into the eye, and/or to employvarious procedures for establishing, restoring, or increasing blood flowto the eye.

The present invention also includes a method for treating an ophthalmicartery, comprising: forming a penetration in a wall of a carotid artery;positioning an arterial access sheath through the penetration; causingretrograde blood flow from the ophthalmic artery into the sheath. Insome embodiments, the method may also include inserting a deliverycatheter through the sheath into a treatment site comprised of theinternal carotid artery, the ostium, the junction between the ICA andthe OA, the portion of the OA near the ICA, and/or the ophthalmicartery. In this aspect, causing retrograde flow may comprise connectingthe arterial access sheath to a passive flow reversal circuit, or it maycomprise connecting the arterial access sheath to an active aspirationsource such as a syringe or suction pump.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is an exemplary illustration of a system of devices fortranscervical ophthalmic artery procedures using a retrograde blood flowembolic protection system, wherein an arterial access device accessesthe ophthalmic artery via a transcervical approach and a venous returndevice communicates with the internal jugular vein.

FIG. 2 shows an embodiment of an arterial access device.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is an apparatus, system, and method of treatmentof eye disease using any apparatus or system that involves reverse bloodflow or retrograde blood flow. Preferred embodiments of the apparatus,system, and methods induce reverse blood flow or retrograde blood flowin one or more arteries, including but not limited to the ophthalmicartery (OA).

As used herein, reverse flow or retrograde flow refers to theconsequences of blocking blood flow in an artery and establishing afluid flow connection with a vein. Under these conditions, the naturalpressure gradient differential causes blood to flow in a reversedirection in the artery. For example, when flow through the internalcarotid artery is blocked, the natural pressure gradient between theinternal carotid artery and the venous system causes blood to flow in aretrograde or reverse direction from the vasculature of the eye, throughthe OA, and through the internal carotid artery.

In some embodiments of the invention, retrograde blood flow may beestablished between an artery and a vein. In preferred embodiments, areverse flow or retrograde system may be established in any locationsuitable for treatment of eye disease. These locations include but arenot limited to the internal carotid artery, the external carotid artery,the common carotid artery, the supraorbital artery, the supra-trochlearartery, the ophthalmic artery; and an appropriate site in the venoussystem, including but not limited to the internal jugular vein or thefemoral vein.

In some embodiments of the invention, retrograde flow is used incombination with other medical procedures and devices to access, treat,and/or deploy a medical device in the fluid flow path between the ICAand the eye. As used herein, fluid flow path refers to a section of theICA, the ostium, the OA, and other arteries that supply blood to theeye.

A reverse flow system may be variously configured and include a widenumber of elements and devices. The typical reverse flow system includesan access device or port into an artery, an access device or port into avein, one or more tubes or conduits connecting the two access ports, andan occlusion device (e.g., balloon or clamp or the like).

Exemplary reverse and/or retrograde blood flow devices and systemsinclude, but are not limited to U.S. Pat. Nos. 9,259,215; 9,241,699;9,265,512; 8,545,432; 7,927,347; 7,235,095; 6,936,060; 6,929,634;6,908,474; 6,905,490; 6,902,540; 6,855,162; 6,827,726; 6,824,558;6,645,222; 6,641,573; 6,540,712; 6,423,032; 6,413,235; 6,344,054;6,336,933; 6,302,908; 5,820,595; 5,709,701; and US. Patent applications20090024072; 20110160762; all of which are incorporated by reference intheir entirety.

None of these patents and applications teach the use of reverse flow totreat eye diseases or conditions, or to access the ophthalmic artery.

In accordance with an embodiment of the present invention, eye diseasemay be treated using at least one arterial access device and aretrograde flow system, using a percutaneous transfemoral approach; atranscervical approach; cervical access; or combinations thereof. Thepreferred embodiments of the invention use a femoral or cervicalapproach.

In order to reverse blood flow in the Common Carotid Artery (CCA) duringinterventional procedures, creation of a circuit is necessary to extractblood from the CCA and return it to a venous location. Extracting bloodfrom the CCA and returning it to a venous location takes advantage ofcompensatory blood flow through the circle of Willis, high pressure ofthe arterial system and low pressure of the venous system. Reversingblood flow allows for filtration of the blood so that particulatesgenerated during an interventional procedure are removed fromcirculation thereby preventing/reducing the possibility of an embolicevent. Several structures are typically required to create the reverseblood flow circuit: 1) an Artery Sheath which provides access to theartery; 2) an arterial occlusion device, typically catheter based, whichis inserted into the artery via the sheath. This device will incorporatea distal inflatable element, typically similar in design to anangioplasty balloon, which is designed to be positioned into the arteryand inflated. The balloon is dimensionally designed to occlude theartery such that normal antegrade blood flow will be stopped upon fullinflation and forced through one of the device lumens during the reverseflow portion of the procedure. This device will have one or more thrulumens capable of carrying blood and inserting medical instruments aswell as a port (stopcock) for accessing these lumens and connecting to avenous entry for returning the blood. 3) A Venous Sheath. This sheathprovides access to the venous system and may include a port (stopcock)for connecting to the circuit to serve as the return point for thearterial blood. 4) A blood filter. This filter is designed withmicropores that filter out particulate, but allow blood to flow from oneside to the other. This filter may have lure connecters on each end toallow for connection to the reverse flow circuit. 5) IV lines. Theselines connect the occlusion device port (stopcock) to the filter and thefilter to the venous sheath port (stopcock).

One or more methods of the present invention include but are not limitedto inserting and/or delivering an arterial access device to a desiredartery and position, blocking flow in the artery, and allowingretrograde or reverse flow to cause blood to flow in a reverse orretrograde flow direction and into a shunt. The retrograde blood flowmay then be directed through the venous return device into a vein.

Some embodiments of the invention include high flow capacity, one aspectof which may be a delivery apparatus having a large bore. Having a largebore also may include a large internal dimension, useful for example, indelivering and using certain transcatheter devices.

One skilled in the art will recognize that lumen size for the system(circuit) components (include catheters, sheaths, stopcocks and filters)may be optimized for a particular location and/or circuit. Average CCAdiameters can be in the 6.0 mm/18 Fr (or larger) range and average IJVdiameters can be in the 13 mm/>Fr 34 (or larger) range. Larger than 2.66mm/Fr 8 to accommodate these artery/vein sizes may also be used.

One skilled in the art will recognize that pore size of one or morefilters may be optimized and/or coordinated in order to achievemedically appropriate filtration. In accordance with some embodiments ofthe invention, the system may include one or more filters; in systemshaving more than one filter, the pore size of the filters may be thesame or different.

According to some embodiments of the invention, the circuit may beoptimized for length. The inventors believe that carotid access may bebeneficial, in part because of a circuit in which the guidewire may beapproximately 15 inches in length.

In some embodiments of the invention, the reverse flow system is used toaccess or treat an arterial area or segment between the ICA and the eye.Such treatment includes but is not limited to removing a blockage. Insome embodiments, treatment includes restoring or increasing blood flowto the eye. In preferred embodiments, the treatment, apparatus, orsystem removes a blockage or constriction in the OA near the ICA, e.g.,in the ostium and/or in the first section of the OA before the sharpbend in the artery.

Restoring and/or increasing blood flow is used herein to refer to anydevice, method, therapy, or combination that changes the blood flow tothe eye. Examples of such include, but are not limited to increasing theblood flow anywhere in the vasculature leading to the eye or a portionof the eye; removing or opening an obstruction in the fluid flow path inthe vasculature leading to the eye, e.g., from the ICA through the OA;delivering and deploying a stent in the fluid flow path in thevasculature leading to the eye; using atherectomy or similar devices tophysically remove portions of any obstructions in the vasculatureleading to the eye or portion of the eye; and localized drug and/or anoxygen device for increasing flow or amount of oxygen in one or more eyetissues. In some an embodiments, a device or method of the presentinvention may be combined with a known or new drug or oxygen device inorder to treat one or more eye diseases or conditions.

The present invention may also include restoring and/or increasing theamount of nutrients that is available to one or more parts of the eye orto the eye area, specifically by removing or partially opening ablockage in one or more of the arteries that supplies blood flow to theeye. In preferred embodiments of the invention, a blockage is removed oropened in the Internal Carotid Artery, the Ophthalmic Artery, the ostium(as used herein, referring to the junction between the ICA and the OA),or combinations thereof. To or near the eye, as used herein, refers tothe vasculature system that supplies blood to the various structures ofthe eye. As noted above, nutrients as used herein includes but is notlimited to oxygen, hemoglobin, complement, and glucose.

The present invention may also include methods, devices, and systems forremoving a blockage in the ostium or a proximal segment of the OA nearthe ICA. In these embodiments, removing the blockage comprises opening achannel or access through the ostium sufficient to provide atherapeutically beneficial result to the eye, the rear of the eye, orportions thereof. The present invention also includes restoring and/orimproving blood flow anywhere in the vascular pathway to or within theeye.

Therapeutically beneficial result is used herein to refer to anyperceived or actual benefit to the patient. Examples of beneficialresults include but are not limited to: treatment of an eye disease,condition, and/or symptom; restoring or increasing blood flow in anymanner that treats an eye disease, condition, and/or symptom; andremoving or partially removing a blockage in the blood flow path betweenthe heart and the eye, preferably in the ophthalmic artery or a portionthereof.

Applicants and inventors intend that the invention should not be limitedsolely to changing vascular flow in order to improve or restore theamount of nutrients that are delivered to the eye. For example, in someembodiments of the invention, the vascular flow may be unaffected forthe most part, but the amount or concentration of nutrients may beincreased, thereby increasing the amount of nutrients that may bedelivered to the eye or associated with the eye. One skilled in the artmay recognize, with the teaching of this invention, that there are otherbiological systems or capabilities that may be used to increase theamount of nutrients that are delivered to the eye.

In this and other embodiments of the invention, reducing blockageincludes but is not limited to piercing or penetrating the blockage. Inmost preferred embodiments of the invention, piercing and penetratingthe blockage refers to obtaining sufficient blood and/or fluid flowthrough or around the blocked vascular area sufficient to provide atherapeutically beneficial amount of oxygen to the eye or a portion ofthe eye.

Some embodiments of the present invention include a retrograde flowsystem that does not require the use of a balloon or the like. In theseballoonless systems, methods, and assemblies the flow direction elementmay be an external force applied to an artery to compress the arteryaround the sheath. As used herein, external force refers to any elementor structure that functions to apply force, to clamp or close the arteryagainst the sheath. Exemplary elements include, but are not limited to aclamp, vise, band, suture, pincer, contractor, constrictor, and thelike. In function, any such element compresses or closes the arteryagainst the sheath or tube, thereby forcing any blood flow through thelumen of the tube rather than around the tube.

An embodiment of the inventions includes methods and devices fortreating a non-human animal. Some embodiments of the invention includetreating a dog, including but not limited to treating central serousretinopathy.

In accordance with the present invention, a reverse flow system may bevariously configured and include a variety of elements and components.Typical components and elements include, but are not limited to: anarterial access device; a venous return device; one or more shunts; aflow control assembly; an arterial port; a venous port; a shunt valve; aflush line; one or more shut off valves; one or more connectors; one ormore tubing members; one or more syringes; one or more vessel closuredevices; one or more suture delivery devices; one or more interventionalcatheters; one or more interventional delivery devices; one or moreexternal receptacles; one or more adapters; one or more Y connectors; aflow state indicator; a flow rate activator, one or more sensors; atimer; contrast; one or more stopcocks; one or more manifolds.

The invention may also include a delivery system configured or adaptedto position and/or orient a medical device in the OA; atherectomy orangioplasty in the OA; all in combination with a reverse flow system.

The retrograde flow system 100 can include the arterial access device110, venous return device 115, and shunt 120 which provides a passagewayfor retrograde flow from the arterial access device 110 to the venousreturn device 115. The system also may include the flow control assembly125, which interacts with the shunt 120 to regulate and/or monitorretrograde blood flow through the shunt 120. Embodiments of thecomponents of the retrograde flow system 100 are described below.

FIG. 1 shows an exemplary embodiment of a retrograde flow system 100that is adapted to establish and facilitate retrograde or reverse flowblood circulation in the ophthalmic artery in order to limit or preventthe release of emboli into the eye. The system 100 interacts with theophthalmic artery to provide retrograde flow from the vasculature of theeye to a venous return site, such as the internal jugular vein (or toanother return site such as another large vein or an external receptaclein alternate embodiments.) The retrograde flow system 100 can include anarterial access device 110, a venous return device 115, and a shunt 120that provides a passageway for retrograde flow from the arterial accessdevice 110 to the venous return device 115.

An optional flow control assembly 125 can interact with the shunt 120.The flow control assembly 125 can be adapted to regulate and/or monitorthe retrograde flow from the ophthalmic artery to the internal jugularvein. Optionally, the flow control assembly can be replaced with or usedin conjunction with an in-line filter. The flow control assembly 125 caninteract with the flow pathway through the shunt 120, either external tothe flow path, inside the flow path, or both.

The illustrated embodiment shows occluding the CCA. In preferredembodiments the occlusion element is positioned in and occludes the ICAand/or the OA.

The arterial access device 110 can at least partially insert into theinternal carotid artery (ICA) and/or the ophthalmic artery (OA) and thevenous return device 115 at least partially inserts into a venous returnsite such as the internal jugular vein (IJV). The arterial access device110 and the venous return device 115 couple to the shunt 120 atconnection locations 127 a and 127 b. When flow through the ICA isblocked, the natural pressure gradient between the internal carotidartery and the venous system can cause blood to flow in a retrograde orreverse direction from the eye vasculature through the ophthalmic arteryand the internal carotid artery, and through the shunt 120 into thevenous system. The flow control assembly 125 can modulate, augment,assist, monitor, and/or otherwise regulate the retrograde blood flow.

In an alternative embodiment, the flow control assembly may be replacedwith an inline blood filter; or the flow control assembly may be used incombination with an inline blood filter.

In the embodiment of FIG. 1, the arterial access device 110 can accessthe common ophthalmic artery CCA via a transcervical approach.Transcervical access provides a short length and non-tortuous pathwayfrom the vascular access point to the target treatment site therebyeasing the time and difficulty of the procedure, compared for example toa transfemoral approach. Additionally, this access route reduces therisk of emboli generation from navigation of diseased, angulated, ortortuous ICA or OA anatomy. At least a portion of the venous returndevice 115 can be placed in the internal jugular vein IJV. In anembodiment, transcervical access to the ophthalmic artery is achievedpercutaneously via an incision or puncture in the skin through which thearterial access device 110 is inserted. An occlusion element 129, suchas an expandable balloon, can be used to occlude the ICA or OA at alocation proximal of the distal end of the arterial access device 110.The occlusion element 129 can be located on the arterial access device110 or it can be located on a separate device. In an alternateembodiment, the arterial access device 110 accesses the ICA and the OAvia a direct surgical transcervical approach. In the surgical approach,the ophthalmic artery can be occluded using a tourniquet 2105. Thetourniquet 2105 is shown in phantom to indicate that it is a device thatis used in the optional surgical approach.

Some embodiments of the present invention include an arterial accessdevice adapted and configured for use only with an interventionalreverse flow system. In these embodiments, there is no need for avascular surgeon or cut-down procedure. In devices, methods, and systemsaccording to this embodiment, a neuroradiologist or interventionalist isthe only type of physician required to perform the procedure.

In this embodiment, an example of which is shown in FIG. 2, the arterialaccess device or system 111 includes a device delivery system 115, whichmay include an occlusion element 129, such as a balloon or expandablemember, to block the blood flow; a conduit 112 or catheter having alumen through which retrograde blood may pass (RG); and a guidewire 114.The access device or system 111 also includes a sheath 113 having adistal end 116 configured to be flush with the internal wall of theartery and located in a position near but above the occlusion element129.

In the illustrated embodiment, the sheath accesses the artery through askin puncture in the neck (not a surgical cut-down), and the catheteraccesses the artery through a cut-down procedure. In preferredembodiments of the invention, the sheath accesses the artery through askin stick in the neck and the interventional catheter accesses theartery through a femoral access in the groin.

For any of the embodiments of the arterial access device, the sheath isadapted to be introduced through an incision or puncture in a wall of acommon carotid artery, either an open surgical incision or apercutaneous puncture established, for example, using the Seldingertechnique. The length of the sheath can be in the range from 5 to 15 cm,usually being from 10 cm to 12 cm. The inner diameter can be in therange from 7 Fr (1 Fr=0.33 mm) to 10 Fr, usually being 8 Fr.

The illustrated embodiment shows reverse flow through the catheter.Alternatively, reverse blood flow may pass through the sheath. Inpreferred embodiments of the invention, reverse flow can occur througheither the sheath or the catheter, and procedure devices can passthrough whichever of the sheath or catheter that is not being used forreverse flow.

This configuration provides many advantages and alternatives. Reverseflow can pass through the conduit, the sheath, or both. The conduit maybe connected to a shunt, receptacle bag, or vein (e.g., IJV or femoralvein). The catheter comprising conduit 112 may be used without impingingthe function of the sheath, and vice-versa. As noted above, a vascularsurgeon is not required. Also this access device configuration issuitable for use with a cervical (carotid) or femoral access. In apreferred embodiment, access is cervical, primarily because such alocation saves approximately ten minutes procedure time over femoralaccess, thus reducing the patient time in surgery and decreasing theamount of time the patient is subject to stroke risk.

The arterial access device can have various features particularly usefulin a retrograde blood flow system. As shown in FIG. 1, the arterialaccess device 110 can include a flow lines 615 and 915 and a Y-adaptorto connect the sheath to a retrograde flow system. Optionally, thedistal sheath may include an occlusion element 129 for occluding flowthrough, for example the common carotid artery. If the occluding element129 is an inflatable structure such as a balloon or the like, the sheathcan include an inflation lumen that communicates with the occlusionelement 129. The occlusion element 129 can be an inflatable balloon, butit can also be an inflatable cuff, a conical or other circumferentialelement which flares outwardly to engage the interior wall of thecarotid artery to block flow, a membrane-covered braid, a slotted tubethat radially enlarges when axially compressed, or similar structurewhich can be deployed by mechanical means, or the like. In the case ofballoon occlusion, the balloon can be compliant, non-compliant, andelastomeric; reinforced; or have a variety of other characteristics. Inan embodiment, the balloon is an elastomeric balloon which is closelyreceived over the exterior of the distal end of the sheath prior toinflation. When inflated, the elastomeric balloon can expand and conformto the inner wall of the carotid artery. In an embodiment, theelastomeric balloon is able to expand to a diameter at least twice thatof the non-deployed configuration, frequently being able to be deployedto a diameter at least three times that of the un-deployedconfiguration, more preferably being at least four times that of theun-deployed configuration, or larger.

In some embodiments of the invention, the arterial access device mayinclude a catheter having a backstop; a balloon, typically attached to acentral guidewire; and a knot or the like (some other geometricallyshaped element) extending on the guidewire outwardly and distally fromthe balloon. In use, the knot may be deployed in the region of theplaque or obstruction; the knot may be used to loosen particles in theartery, which flow back toward backstop and/or catheter. The balloon maythen be partially deployed, whereby particles may become trapped betweenthe balloon and the end of the catheter (or backstop). The balloon maythen be drawn back into the catheter, thereby drawing and capturingparticles within the lumen of the catheter. The catheter, carrying theparticles, may then be pulled out of the body.

Alternative elements or structures of the system described in theinvention may include a guidewire with a distal tip comprising a kitetail shaped element; a backstop comprising a funnel shaped cage; aballoon that is deployed and/or expanded in stages, e.g., the proximalend first, thereby forcing, pushing, or capturing particles into thebackstop.

The system 100 is adapted to regulate retrograde flow in a variety ofmanners. Any combination of the pump, valve, syringe, and/or variableresistance component can be manually controlled by the user orautomatically controlled via a controller to adjust the retrograde flowrate. Thus, the system 100 can regulate retrograde flow in variousmanners, including controlling an active flow component (e.g., pump,syringe, etc.), reducing the flow restriction, switching to anaspiration source (such as a pre-set VACULOK syringe, VACUTAINER,suction system, or the like), or any combination thereof

Methods of Use

Initially, the distal sheath of the arterial access device 110 isintroduced into a carotid artery and into the internal carotid artery.As noted above, entry into the carotid artery can be via a transcervicalor transfemoral approach, or any approach suitable for introducing adistal portion of a catheter into the ophthalmic artery. After thesheath of the arterial access device 110 has been introduced into theinternal carotid artery, the blood flow will continue in antegradedirection with flow from the ophthalmic artery entering both theinternal carotid artery ICA and the external carotid artery ECA.

The venous return device 115 can then be inserted into a venous returnsite, such as the internal jugular vein IJV. The shunt 120 can be usedto connect the flow lines 615 and 915 of the arterial access device 110and the venous return device 115, respectively (as shown in FIG. 1). Inthis manner, the shunt 120 provides a passageway for retrograde flowfrom the atrial access device 110 to the venous return device 115. Inanother embodiment, the shunt 120 can connect to an external receptaclerather than to the venous return device 115.

Once all components of the system are in place and connected, flowthrough a carotid artery, ICA, or OA can be stopped, such as using theocclusion element 129 as shown in FIG. 1. The occlusion element 129 canbe expanded at a location proximal to the distal opening of the sheathto occlude the OA. Alternately, the tourniquet 2105 or other externalvessel occlusion device can be used to occlude the ophthalmic artery tostop flow. In an alternative embodiment, the occlusion element 129 canbe introduced on second occlusion device 112 separate from the distalsheath 605 of the arterial access device 110. The OA can also beoccluded with a separate occlusion element, either on the same device110 or on a separate occlusion device.

At that point retrograde flow from the OA and internal carotid arteryICA can begin and can flow through the sheath, the flow line 615, theshunt 120, and into the venous return device 115 via the flow line 915.The flow control assembly 125 can regulate the retrograde flow asdescribed above. While the retrograde flow is maintained, a stentdelivery catheter can be introduced into the sheath. The deliverycatheter can be introduced into the sheath through a hemostasis valveand the proximal extension of the arterial access device 110. Thedelivery catheter can be advanced into the internal carotid artery ICAand the OA.

Vibrating Guidewire

Some embodiments of the present invention may include a conventionalguidewire; some embodiments of the invention include a guidewire with abasket or the like on the distal end; other embodiments of the inventionmay include a guidewire having a geometrically shaped element on thedistal end.

This guidewire is intended for neuro interventional procedures in whicha reverse flow system is in use. The guidewire is designed to be used incervical access where there is need to remove plaque from a specificarterial segment. Once reverse flow is established, the guidewire isplaced in the location of the stenosis and a vibration is induced via anelectric motor. This vibration may loosen material either due to directcontact with general vibration, or with contact and by use of a specificresonance frequency of the target material for removal. The guidewire isof general design, however it is optimized for cervical accessprocedures and is designed to fit within the vibratory motor housing insuch a way as to contact the motor. Contact with this motor imparts avibration in the guidewire which is transmitted to the target anatomyand serves to aid in the removal of plaque.

In preferred embodiments of the invention the vibratory motor ispositioned on and or attached to a surgical drape. It is intended thatthe vibratory motor should remain substantially stationary. Theguidewire passes through or is attached to the vibratory motor.Positioning in the target anatomy is accomplished by moving theguidewire in and out of the arterial segment being treated.

Vibrating Angioplasty Balloon

A balloon according to these embodiments of the invention may be aconventional balloon or may include geometric features intended tofacilitate plaque/obstruction removal or dislodgement. Balloons may beof any of a variety of shapes (asymmetrical, spiral, etc.) and/or coatedwith materials for facilitating plaque removal (abrasives, etc.).

This balloon is intended for neuro interventional procedures in which areverse flow system is in use. The balloon is designed to be used incervical access where there is need to remove plaque from a specificarterial segment. Once reverse flow is established, the balloon isplaced in the location of the stenosis and a vibration is induced via anelectric motor. This vibration may loosen material either due to directcontact with general vibration, or with contact and by use of a specificresonance frequency of the target material for removal. The balloon isof general design, however it is optimized for cervical accessprocedures and is designed to fit within the vibratory motor housing insuch a way as to contact the motor. Contact with this motor imparts avibration in the balloon which is transmitted to the target anatomy andserves to aid in the removal of plaque.

In accordance with the present invention, the vibratory balloon, and/orthe vibratory guidewire may loosen plaque or an obstruction, andplaque/obstruction particles and the like may be removed from the siteusing the reverse flow system.

In another embodiment, a medical device or agent is capable ofdelivering drugs to the ostium for the purpose of improving vascularblood flow at the ostium and within the OA. These drugs may include (butare not limited to) low dose Viagra (or equivalent PDE 5 inhibitor),Lucentis, Avastin, Taxol, Rapamyacin or other pharmaceuticals used toimprove vascular blood flow.

Embodiments of the present invention and the various components orelements thereof can be used interchangeably so that features andfunctions of one exemplary embodiment of a filter device can be usedwith other embodiments of the filter device. Additionally, methods ofusing one embodiment of the present invention can be used with otherembodiments of the present invention.

While this specification contains many specifics, these should not beconstrued as limitations on the scope of an invention that is claimed orof what may be claimed, but rather as descriptions of features specificto particular embodiments. Certain features that are described in thisspecification in the context of separate embodiments can also beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment canalso be implemented in multiple embodiments separately or in anysuitable sub-combination. Moreover, although features may be describedabove as acting in certain combinations and even initially claimed assuch, one or more features from a claimed combination can in some casesbe excised from the combination, and the claimed combination may bedirected to a sub-combination or a variation of a sub-combination.Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults.

Although embodiments of various methods and devices are described hereinin detail with reference to certain versions, it should be appreciatedthat other versions, embodiments, methods of use, and combinationsthereof are also possible. Therefore the spirit and scope of theappended claims should not be limited to the description of theembodiments contained herein.

EXAMPLES Example 1

The inventors believe that compromised blood flow to the vasculature ofthe posterior eye directly contributes to diseases of the eye. This lackof normal blood flow may originate in the internal carotid artery (ICA),the ophthalmic artery (OA), branches of the ophthalmic artery, have acardiac origin, and/or combinations thereof, and be directly caused by ablockage in one or more of these vessels. This lack of sufficient bloodflow directly contributes to inadequate nutrient levels seen in tissuessuch as the choroid, retina, optic nerve and other ophthalmic anatomy.This blockage may manifest as stenosis, lesions or other physiologywithin the ophthalmic related vasculature and compromise normal bloodflow such that the posterior eye vasculature does not receive anadequate nutrient supply for maintenance of normal function. As a resultit is possible for a cascade of events to initiate which may result invarious diseases of the eye.

Linear and volumetric blood flow was measured for healthy controls anddiseased patients (with confirmed AMD diagnosis). Flow rates weremeasured for the Left Ophthalmic Artery (LOA), Right Ophthalmic Artery(ROA), Left Internal Carotid Artery (LICA) and Right Internal CarotidArtery (RICA) using Phased Contrast Magnetic Resonance Imaging (PCMRI)technique on a 7 Tesla Nmri machine. These flow rates were measured incm/sec for linear flow and in mi/min for volumetric flow. The averagediameter of the ICA for a healthy control is 46 mm and the averagediameter of the OA for a healthy control is 12 mm. Average values forthe same vessels in diseased patients were 4.18 mm for the ICA and 0.86mm for the OA.

Specific linear and volumetric flow rates were compared, and the OA flowdata shows a medically or clinically observable difference between theflow rates for healthy controls compared to diseased patients. Specificflow rates were compared, and the ICA flow data shows a medically orclinically observable difference between the flow rates for healthycontrols compared to diseased patients. In every case, the blood flowrate for the diseased patients appears to be lower than the blood flowrate for the healthy controls.

Example 2

In a cadaveric tissue, we removed the right ICA and visually examinedthe ostium. We confirmed blockage of the OA at the ostium (whichappeared to be complete). Once the section of left ICA was removed, wewere able to gain internal access to the OA ostium and insert a microPTCA balloon catheter. We performed this test to visually observe theeffect of placing and inflating a balloon catheter in the OA. This(non-compliant) balloon catheter has a maximum diameter of 0.85 mm at 16atms, with a crossing profile of 0.74 mm and a working length ofapproximately 5 mm. We inflated the balloon several times toapproximately 12 atms max and observed the balloon through the vessel.The vessel appeared to tolerate the inflations without obvious damage.

Example 3

A system of the present invention is designed to induce reverse bloodflow in the cerebral vasculature during neuro interventional procedures.This system provides protection from particulate related stroke duringthese procedures. Enhancements to the basic system include:

-   -   Common carotid artery to internal jugular vein circuit. This        pathway reduces the overall device length required to reach the        target anatomy. While this procedure requires cervical access,        there is no need to do femoral access and expose the patient to        the potential issues related to crossing the arch. This type of        connection between an artery and vein is commonly referred to as        a fistula.    -   Addition of an in line filter to capture particulate.    -   Sizing the tubing, stock cocks and filter such that a minimal        resistance to flow is encountered by blood as it travels through        the device. It is anticipated the device will be 8.5 to 9.0        French. Maximizing the internal diameter of the various        components allows for blood to flow at the most rapid velocity.    -   Addition of a circuit to connect the CCA flow to the supra        orbital artery. This connection will provide flow directly to        the OA so that flow is reversed. This OA reverse flow will        prevent embolization of the OA/central retinal artery during        interventional procedures.    -   Specially designed CCA occlusion balloon designed to reduce        probability of low or no flow zones in the CCA.

Example 4

In some embodiments of the invention, this flow direction element of thesystem is used to initiate the reversal of flow in the Common CarotidArtery (CCA). Typically, CCA flow reversal may be accomplished by use ofan inflatable balloon device. CCA flow reversal may also be accomplishedwithout the need for a balloon by using a sheath that has external forceapplied to compress the CCA against the tube portion of the sheath. Thiscompressive action serves to prevent blood flow around the sheath (inthe same way as an inflatable balloon does from inside the CCA) andforce blood through the sheath and into the venous circuit of thesystem, thereby providing flow reversal. The sheath may be ofconventional design, or may contain elements that facilitate compressingthe CCA against the sheath for the purpose of establishing flowreversal.

Methodology and Purpose of Examples 5 and 6:

1) Dissection of specimens diagnosed with AMD for the purpose ofidentifying CAD disease (plaque) in the carotid siphon/ophthalmic ostiumand to provide evidence of the ability to cannulate and deliver anangioplasty balloon to the ophthalmic artery ostium.2) Dissection of a specimen (with cervical segment) diagnosed with AMDto identify CAD disease (plaque) in the carotid siphon/ophthalmicostium.Terminology: OA—Ophthalmic artery; LOA—Left ophthalmic artery; ROA—RightOphthalmic artery; ICA—Internal carotid artery; LICA—Left internalcarotid artery; RICA—Right internal carotid artery; CCA—Common carotidartery; LCCA—Left common carotid artery; RCCA—Right common carotidartery; Cow—Circle of Willis

A true endovascular approach requires an imaging modality that relies oninjection of contrast, which is not possible in static tissue samplessuch as a cadaver. Based on these limitations, the following twoExamples show balloon placement and inflation directly in the exposedophthalmic ostium in situ and post dissection.

Example 5

The primary goal for dissection of a specimen with bilateral AMD was toprove that it is possible to place and dilate an angioplasty ballooncatheter in the segment of the OA just distal to the ICA ostium, priorto the typical OA 90° bend, without dissecting the OA.

We used an angioplasty balloon that has a maximum inflated diameter of0.8 mm at 16 ATMs, and a working length of approximately 3.5 mms.

We identified the left and right internal carotid artery(ICA)/Ophthalmic Artery (OA) ostiums in the first specimen and removedmaterial from the sphenoid to expose the ophthalmic artery (OA). Wepositioned the balloon catheter into the left OA (LOA) and inserted theballoon such that the working length of the balloon did not extendbeyond the desired segment of the LOA.

The balloon was able to be delivered and inflated at the desiredlocation of the LOA, within the ostium of the LOA.

We then examined both ostiums for evidence of plaque in the ICA, OA, andostium in situ. We identified plaque formation at the ostium of thetransected LICA, and plaque formation in the walls of the LICA.Likewise, we also identified plague formation in the RICA, at the ostiumof the transected ROA and in the walls of the RICA.

We were able to successfully position and inflate an angioplasty balloonwithin the target LOA anatomy. We were also able to identify plaqueformation in both the LICA and RICA as well as both the ROA and LOAostium.

Example 6

The primary goal for dissection of this specimen was to prove that it ispossible to place and dilate an angioplasty balloon catheter in thesegment of the OA just distal to the ICA ostium, prior to the typical OA90° bend, without dissecting the OA. The secondary goal was to examineeach ICA/OA ostium for evidence of plaque. We identified the left andright ICA/OA ostiums without having to remove material from the sphenoidand could visualize plaque in both ICA segments in situ. In addition, wecould clearly see plaque formation in the LOA.

We removed both the left and right ICA vessel segments and transectedeach. In both samples, we observed blockage directly at the ophthalmicostium.

We examined both the inside and outside of the LICA vessel. We couldclearly see a plaque formation at the base of OA near the ostium. Wedissected the LOA from the LICA at the ostium to expose the plaque. Theplaque formation was clearly seen in the ostium of the LOA.

We used the RICA vessel segment to place the balloon catheter. Theballoon catheter was positioned into the ROA and inserted such that theworking length of the balloon did not extend beyond the desired segmentof the ROA (as noted in the previous Example).

We were able to successfully position and inflate an angioplasty balloonwithin the target ROA anatomy. We were also able to identify plaque inboth the LICA and RICA as well as both the ROA and LOA ostium. Thisplaque appeared to be blocking or nearly blocking the OA in both theleft and right ostiums.

1-9. (canceled)
 10. A method, comprising: inducing retrograde flow in anartery, to stop antegrade flow in an ophthalmic artery of a subject;positioning a first device within the ophthalmic artery; treating atleast one of the ophthalmic artery or a junction between an internalcarotid artery and the ophthalmic artery of the subject, with the firstdevice; and delivering the induced retrograde flow to the venous systemof the subject.
 11. The method of claim 10, wherein inducing retrogradeflow in the artery includes intravascularly inducing retrograde flow inthe artery.
 12. The method of claim 10, wherein inducing retrograde flowin the artery causes retrograde flow in the ophthalmic artery.
 13. Themethod of claim 10, further including: restoring antegrade blood flow inthe ophthalmic artery.
 14. The method of claim 10, further including:increasing nutrient delivery to the ophthalmic artery.
 15. The method ofclaim 10, wherein positioning the first device within the ophthalmicartery of a subject includes extending the first device through a lumenof another device located within an arterial system of the subject. 16.A method, comprising: intravascularly introducing a first device into asubject, the subject having an ophthalmic artery with a first antegradeblood flow rate therein; inducing retrograde blood flow in a carotidartery; positioning the first device within the ophthalmic artery;without the first antegrade blood flow in the ophthalmic artery,treating tissue of the ophthalmic artery or a junction of an internalcarotid artery and the ophthalmic artery, via the first device; andafter treating tissue, ceasing retrograde blood flow in the carotidartery.
 17. The method of claim 16, wherein, after ceasing retrogradeblood flow, the ophthalmic artery has a second antegrade blood flow rategreater than the first antegrade blood flow rate.
 18. The method ofclaim 16, further including increasing nutrient delivery to theophthalmic artery.
 19. The method of claim 16, wherein treating tissueof the ophthalmic artery or the junction of the internal carotid arteryand the ophthalmic artery includes removing tissue of at least one of alesion or a blockage.
 20. The method of claim 19, wherein the inducingthe retrograde blood flow includes inducing retrograde flow distal ofthe at least one of the lesion or the blockage.
 21. The method of claim16, further including: positioning a second device within a venoussystem of the subject; and delivering the induced retrograde blood flowto the venous system via the second device.
 22. The method of claim 16,further including filtering the induced retrograde blood flow.
 23. Amethod, comprising: inducing retrograde flow in an ophthalmic artery ofa subject; positioning a first device within the ophthalmic artery ofthe subject; and filtering the induced retrograde flow.
 24. The methodof claim 23, further including: positioning a second device within aninternal carotid artery of the subject.
 25. The method of claim 24,wherein positioning the first device within the ophthalmic artery of thesubject includes delivering the first device through a lumen of thesecond device.
 26. The method of claim 23, further including: ceasingthe retrograde flow in the ophthalmic artery of the subject.
 27. Themethod of claim 23, further including: delivering the filtered inducedretrograde flow to a venous system of the subject.
 28. The method ofclaim 23, wherein the inducing retrograde flow in the ophthalmic arteryincludes occluding an internal carotid artery of the subject.
 29. Themethod of claim 23, further including: treating tissue of the ophthalmicartery or a junction of an internal carotid artery and the ophthalmicartery, via the first device.
 30. A method, comprising: positioning afirst device within an ophthalmic artery of a subject, wherein theophthalmic artery has a first antegrade blood flow rate; inducingretrograde blood flow in a carotid artery and the ophthalmic artery;treating tissue of the ophthalmic artery or a junction of the internalcarotid artery and the ophthalmic artery, via the first device; andceasing retrograde blood flow in the carotid artery; wherein afterceasing retrograde blood flow, the ophthalmic artery has a secondantegrade blood flow rate greater than the first antegrade blood flowrate.
 31. The method of claim 30, wherein treating tissue of theophthalmic artery or a junction of the internal carotid artery and theophthalmic artery includes treating tissue of the ophthalmic artery. 32.The method of claim 31, further comprising filtering the retrogradeblood flow during the treating tissue step, wherein filtering theretrograde blood flow includes capturing emboli.
 33. The method of claim30, wherein treating tissue of the ophthalmic artery or a junction ofthe internal carotid artery includes treating at least one of a completeblockage or a partial blockage of an ophthalmic artery via at least oneof a stenting, an angioplasty, an atherectomy, or a drug treatment. 34.The method of claim 30, wherein the first antegrade blood flow rate andthe second antegrade blood flow rate are volumetric blood flow rates.35. The method of claim 30, wherein the first antegrade blood flow rateand the second antegrade blood flow rate are linear blood flow rates.36. The method of claim 30, wherein the second blood flow rate increasesan amount of a nutrient to the eye, relative to an amount of thenutrient to the eye from the first blood flow rate, wherein the nutrientincludes one or more of oxygen, hemoglobin, complement, and glucose. 37.The method of claim 30, wherein inducing retrograde blood flow in theophthalmic artery causes blood flow from an artery to a venous systemvia a connection between the artery and the venous system.
 38. Themethod of claim 37, wherein inducing retrograde blood flow in theophthalmic artery includes occluding the internal carotid artery. 39.The method of claim 30, further comprising controlling the inducing ofretrograde blood flow, via a pump, a syringe, a valve, or an aspirationsource.